Intensive Statin Therapy in Acute Coronary Syndromes and Stable Coronary Heart Disease: A Comparative Meta-Analysis of Randomized Controlled Trials

Jonathan Afilalo ¹, Agnieska A Majdan ¹ and Mark J Eisenberg ^1*

¹ SMBD-Jewish General Hospital, McGill University, Canada

^* To whom correspondence should be addressed. E-mail: markjeisenberg{at}yahoo.com.

Accepted 23 January 2007

Abstract

Background Intensive statin therapy reduces major adverse cardiovascular events (MACE) but the effect on mortality is unclear. Our primary objective was to determine whether intensive statin therapy reduces all-cause mortality compared to moderate statin therapy in patients with recent acute coronary syndromes (ACS) and stable coronary heart disease (CHD).

Methods We searched MEDLINE, EMBASE, the Cochrane Database, the Internet, and conference proceedings from 1966 to 2006 to identify relevant trials. Selection criteria were randomized allocation to intensive statin therapy (atorvastatin 80 mg/d, simvastatin 80 mg/d, or rosuvastatin 20-40 mg/d) versus moderate statin therapy, recent ACS or stable CHD at the time of randomization, and i6 months of follow-up.

Results We pooled 6 trials encompassing 110,038 patient-years. In patients with recent ACS, intensive statin therapy reduced all-cause mortality from 4.6% to 3.5% over 2.0 years (OR 0.75, 95% CI 0.61 to 0.93). In patients with stable CHD, intensive statin therapy had no effect on all-cause mortality over 4.7 years (OR 0.99, 95% CI 0.89 to 1.11). Overall, intensive statin therapy was associated with a reduction in MACE (OR 0.84, 95% CI 0.77 to 0.91) and hospitalizations for heart failure (OR 0.72, 95% CI 0.62 to 0.83). Intensive statin therapy was also associated with an increase in hepatic transaminases >3 times normal (OR 3.72, 95% CI 2.10 to 6.57) and a trend towards increased creatine kinase >10 times normal and/or rhabdomyolysis (OR 1.96, 95% CI 0.50 to 7.63).

Conclusions Compared to moderate statin therapy, intensive statin therapy reduces all-cause mortality in patients with recent ACS but not in patients with stable CHD.

Keywords: cholesterol, coronary disease, lipids, meta-analysis, mortality

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